Overview: This proposal directly addresses a critical public health challenge impacting pregnant and postpartum persons in Zimbabwe: the prevention of HIV acquisition and transmission. Background/Significance: The risk of HIV acquisition increases three- to four-fold in late pregnancy and early postpartum. Oral pre-exposure prophylaxis (PrEP) is safe during pregnancy, effective in preventing HIV, and available in Zimbabwean antenatal care (ANC) clinics. However, PrEP use remains low among cisgender women of reproductive age. Individual-, interpersonal/community-, and provider-level barriers (e.g., psychological distress, stigma, low partner support, limited PrEP knowledge in providers) compromise use. Preliminary studies: In this R34 application, we propose to develop a multi-level PrEP adherence and persistence intervention as an adaptation and extension of our TENDAI (‘grateful’ in Shona) program, a problem- solving approach to reduce depression and increase HIV treatment adherence among people living with HIV in Zimbabwe. To develop TENDAI, we culturally adapted evidence-based adherence strategies and combined them with problem-solving therapy for depression, targeting depressed mood as a pathway to reduced antiretroviral therapy (ART) adherence. In participants randomized to the intervention, TENDAI was associated with increased ART adherence and decreased depression. Therefore, our Zimbabwe-, US-, and UK-based team has the expertise required to extend TENDAI into a multi-level, problem-solving PrEP use intervention (TENDAI4PrEP) for pregnant persons with psychological distress, their partners, and antenatal care providers. Approach: TENDAI4PrEP will support PrEP adherence and persistence during pregnancy among individuals with psychological distress who have agreed to initiate PrEP use. In Aim 1, we will explore the impact of intersecting, multi-level barriers to PrEP uptake, adherence, and persistence among pregnant persons as well as barriers to the provision of PrEP among antenatal care providers. In Aim 2, we will use the formative data to specify the intervention, likely involving a patient component (inclusive of a dyadic session with a partner) and a provider component, and conduct a small proof-of-concept trial. In Aim 3, we will evaluate the feasibility and acceptability (primary outcomes) of (a) the patient-level intervention in a pilot RCT and (b) the provider-level component in a pre-post design. Secondary outcomes of the RCT will be (1) self-reported PrEP adherence and (2) psychological distress, both at the end of treatment, and (3) PrEP persistence (measured via dried blood spots) at 3-month follow-up. Secondary outcomes of the provider component will be PrEP knowledge and PrEP stigma. We will also explore key implementation outcomes among ANC providers and administrators. Outcomes/next steps: These aims will lay the groundwork for a full-scale, hybrid effectiveness/implementation trial which could dramatically improve rates o...